Various methods for detecting the presence of an analyte in a sample of biological fluid through the use of immunochemistry have been described. In the so-called “sandwich” method, for example, a target analyte such as an antigen is “sandwiched” between a labeled antibody and an antibody immobilized onto a solid capillary support. The assay is read by observing the presence and amount of bound antigen-labeled antibody complex. Because such a method discussed below can detect both antibodies and antigens, they are generally referred to as immunochemical antigen-antibody assays or simply binding ligand affinity assay.
Solid phase immunoassay devices provide sensitive detection of an analyte in a biological fluid sample such as a whole blood sample. Solid phase immunoassay devices incorporate a solid capillary support to which one member of a ligand-receptor pair, usually an antibody, antigen, nucleic acid aptamer or hapten, is bound. Common early forms of solid capillary supports were plates, tubes, or beads of polystyrene which were well known from the fields of radio isotopic immunoassay and enzyme immunoassay. More recently, a number of porous materials such as nylon, nitrocellulose, cellulose acetate, glass fibers, PVDF (poly-vinylidene fluoride) and other porous polymers have been employed as solid capillary supports. A number of self-contained immunoassay kits using porous materials as solid phase capillary carriers of immunochemical components such as antigens, haptens, or antibodies have been described.
U.S. Pat. No. 5,073,484 filed on Feb. 23, 1983 discloses a method and apparatus for the quantitative determination of an analyte in a liquid employs a liquid-permeable solid medium defining a liquid flow path. The medium includes a number of reaction-containing reaction zones spaced apart along the flow path and in which reaction occurs with the analyte or an analyte derivative (e.g., a labeled analyte) to result in the formation of a predetermined product. Detector means are employed to detect analyte, analyte derivatives, reactant or predetermined product in the reaction zones. The number of such zones in which such detection occurs indicates the amount of analyte in the liquid.
U.S. Pat. No. 6,020,147 filed on Jun. 1, 1992 discloses a device for detecting the presence of an analyte in a carrier liquid suspected of containing said analyte. The device comprises a liquid permeable solid medium which defines a path for fluid flow capable of supporting capillary flow, along which are i) a site for application of the carrier liquid, ii) a diffusively bound labeled reactant specific for the analyte or a chemical moiety which is itself the reaction product of the analyte with another chemical moiety, said labeled reactant being capable of flowing along the flow path, wherein said diffusively bound labeled reactant and said analyte or chemical moiety are of a specific ligand-receptor (antigen-antibody) pair, and iii) one or more zones spaced along said flow path, each zone having a predetermined amount of a reactant bound to it which is specific for either the analyte or a chemical moiety which is itself the reaction product of the analyte with another chemical moiety. The device can be used by contacting a carrier liquid with said application site in such a manner that permits said liquid to pass along the flow path by capillary flow such that analyte or reaction product of the analyte with another chemical moiety becomes bound to both the labeled reactant and the reactant bound to the solid medium. The labeled reactant, with the reactant bound to the solid medium, sandwiches the analyte or a chemical moiety which is itself the reaction product of the analyte with another chemical moiety.
U.S. Pat. No. 5,713,389 filed on Dec. 23, 1992 discloses a test cell for detection of a pre-selected ligand in a liquid sample such as a body fluid. The test cell includes an elongate outer casing which houses an interior permeable material capable of transporting an aqueous solution and defining a sample inlet, a test volume, and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet and is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and extending from the inlet and through the test volume. In the test volume is a test site which includes a first protein having a binding site specific to a first epitope of the ligand immobilized in fluid communication with the flow path. The test site can be observed through a window of the casing.
U.S. Pat. No. 5,622,871 filed on Jul. 15, 1993 discloses an analytical test device useful for example in pregnancy testing, includes a hollow casing constructed of moisture-impervious solid material, such as plastics materials, containing a dry porous carrier which communicates indirectly with the exterior of the casing via a bibulous sample receiving member which protrudes from the casing such that a liquid test sample can be applied to the receiving member and permeate therefrom to the porous carrier, the carrier containing in a first zone a labelled specific binding reagent is freely mobile within the porous carrier when in the moist state, and in a second zone spatially distinct from the first zone unlabelled specific binding reagent for the same analyte which unlabelled reagent is permanently immobilized on the carrier material and is therefore not mobile in the moist state, the two zones being arranged such that liquid sample applied to the porous carrier can permeate via the first zone into the second zone, and the device incorporating an aperture in the casing, enabling the extent (if any) to which the labelled reagent becomes bound in the second zone to be observed. Preferably the device includes a removable cap for the protruding bibulous member.
U.S. Pat. No. 5,559,041 filed on Jun. 3, 1993 discloses an immunochemical assay device comprising a base member and an array disposed on the base member. The array comprises (i) a reservoir pad having sufficient porosity and volume to receive and contain a liquid sample on which the assay is to be performed; (ii) a wicking membrane disposed distally to said reservoir pad, said wicking membrane having sufficient porosity and volume to absorb a substantial proportion of the sample received in said reservoir pad; and (iii) at least one filter zone which is separate and distinct from said reservoir pad and wicking membrane, and interposed between and contiguous with said wicking membrane and said reservoir pad, said filter zone having impregnated therein a labeled immunochemical component capable of binding to an analyte of interest in said sample to form an immuno-complex, said filter zone being operable to permit passage of any specific immuno-complex to said wicking membrane while impeding passage of larger components contained in said sample. At least one immobilized substance disposed in at least one assay indicia zone of said wicking membrane downstream of said reservoir pad is operable to bind to a specific immuno-complex contained in the sample to form said assay indicia.
U.S. Pat. No. 7,109,942 filed on Feb. 12, 2001 discloses a test device for determination of an analyte in a liquid sample, comprising: (a) a nitrocellulose carrier, (b) a binding reagent effective to capture analyte, when present, in a defined detection zone of the nitrocellulose carrier; (c) a labeled reagent which is freely mobile in the nitrocellulose carrier in the presence of the liquid sample, said labeled reagent being selected such that it is captured in the detection zone when analyte is present in the liquid sample; (d) a sample receiving member; and (e) a control zone, disposed on or in the nitrocellulose carrier on a side of the detection zone remote from the sample receiving member. The control zone comprises a control binding reagent which binds the labeled reagent whether or not analyte is present in the sample. Liquid sample applied to the sample receiving member is transported to and then along the length of the nitrocellulose carrier to pass through the detection zone, and the detection of labeled reagent in the detection zone is indicative of the presence of analyte in the liquid sample.